The ME Association End of Week Research Round-up | 17 April 2020


Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

This information will be included in the monthly update to the central Research Index which is made freely available as a download at the end of every month.

You can also find the Index in the Research section of the website together with a list of Research Summaries from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 10 – 16 April 2020

This week, 4 new research studies have been published, highlights include:

1. A study from Sweden looked into emotional regulation and sleep in ME/CFS patients compared to healthy controls. They found that 70% of patients had increased numbers of awakenings during the night and 22% had sleep apnoea. There were significant differences between patients and controls in several aspects of emotional regulation and they found significant correlations between reduced emotional awareness and number of awakenings.

2. Researchers from Belgium compared signals on an electroencephalogram (EEG) in response to a laser stimulus to study neuropathic pain between CFS patients, chronic whiplash patients and healthy controls. They found no significant differences, which does not support the idea of generalized central nervous system hyperexcitability in these conditions.

3. The ‘EUROMENE’ research group have developed a Europe-wide approach to investigating the economic impact of ME/CFS, facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant.

4. Dr. Cara Tomas’s team from Newcastle University has carried out some further analyses on the data gathered from their recent study on mitochondria in ME/CFS. They found that severely affected patients have reduced glycolysis (the first step in the breakdown of glucose to extract energy for cellular metabolism) compared to moderately affected patients and healthy controls. This sets them apart from moderately affected patients and may explain why they present with a more severe phenotype.

ME/CFS Research references and abstracts

1. Bileviciute-Ljungar I and Friberg D (2020)
Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—A Pilot Study.
Frontiers in Psychiatry 11: 222.

Abstract
Introduction: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography.

Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.

Methods: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.

Result: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.

Conclusion: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.

2. Goudman L et al. (2020)
Processing of Laser-Evoked Potentials in Patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and Healthy Controls: A Case-Control Study.
Pain Medicine [Epub ahead of print].

Abstract
Objective: Laser-evoked potentials (LEPs) are among the reliable neurophysiological tools to investigate patients with neuropathic pain, as they can provide an objective account of the functional status of thermo-nociceptive pathways.

The goal of this study was to explore the functioning of the nociceptive afferent pathways by examining LEPs in patients with chronic whiplash-associated disorders (cWAD), patients with chronic fatigue syndrome (CFS), and healthy controls (HCs).

Subjects: The LEPs of 21 patients with cWAD, 19 patients with CFS, and 18 HCs were analyzed in this study.

Methods: All participants received brief nociceptive CO2 laser stimuli applied to the dorsum of the left hand and left foot while brain activity was recorded with a 32-channel electroencephalogram (EEG). LEP signals and transient power modulations were compared between patient groups and HCs.

Results: No between-group differences were found for stimulus intensity, which was supraliminal for Aδ fibers. The amplitudes and latencies of LEP wave components N1, N2, and P2 in patients with cWAD and CFS were statistically similar to those of HCs. There were no significant differences between the time-frequency maps of EEG oscillation amplitude between HCs and both patient populations.

Conclusions: EEG responses of heat-sensitive Aδ fibers in patients with cWAD and CFS revealed no significant differences from the responses of HCs. These findings thus do not support a state of generalized central nervous system hyperexcitability in those patients.

3. Pheby D et al. (2020)
The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE).
Healthcare 8 (2).

Abstract
We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries.

The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment.

However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it.

We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries.

We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list.

We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.

4. Tomas C et al. (2020)
The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function.
PLoS One 15 (4).

Abstract
Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts.

We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction.

Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function.

Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts.

This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

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